Titre du document / Document title

Effects of donepezil on DOI-induced head twitch response in mice : implications for Tourette syndrome

Auteur(s) / Author(s)

HAYSLETT Renee L. ⁽¹⁾ ; TIZABI Yousef ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Pharmacology, College of Medicine, Howard University, 520 W Street N.W., Washington, DC 20059, ETATS-UNIS

Résumé / Abstract

Tourette syndrome (TS) is a neurological disorder characterized by persistent motor and phonic tics. Administration of the selective 5-HT_2A/2Cagonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) induces head twitches in mice that have been proposed to model tics seen in TS. Previous studies have demonstrated that nicotine markedly attenuates DOI-induced head twitch response (HTR). This and the reports that nicotine may have clinical efficacy in reducing symptoms of TS suggest possible involvement of the nicotinic cholinergic system in this disorder. Donepezil is an acetylcholinesterase inhibitor approved for use in mild to moderate Alzheimer's disease. The purpose of this study was to investigate whether donepezil might also reduce DOI-induced HTR, and whether its combination with nicotine might result in an additive or synergistic effect. Moreover, to elucidate the possible role of nicotinic receptors in this paradigm, the effects of mecamylamine, a nicotinic antagonist, were also evaluated. Acute and chronic administration of donepezil (0.1 mg/kg) or nicotine (0.5 mg/kg base) significantly reduced DOI-induced HTR. No additive or synergistic effects of donepezil and nicotine were observed. Acute mecamylamine administration (0.5-5.0 mg/kg) dose dependently inhibited DOI-induced HTR. None of the mecamylamine doses blocked the inhibitory effects of donepezil or nicotine on DOI-induced HTR. These results suggest that donepezil may have therapeutic potential in treating motor tic symptoms of TS. Moreover, the action of donepezil and nicotine may be mediated through the same mechanism.

Revue / Journal Title

Pharmacology, biochemistry and behavior   ISSN 0091-3057   CODEN PBBHAU 

Source / Source

2003, vol. 76, n^o3-4, pp. 409-415 [7 page(s) (article)] (38 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier Science, New York, NY, ETATS-UNIS  (1973) (Revue)

Mots-clés anglais / English Keywords

Enzyme ; Hydrolases ; Esterases ; Carboxylic ester hydrolases ; Degenerative disease ; Cerebral disorder ; Central nervous system disease ; Nervous system diseases ; Vertebrata ; Mammalia ; Rodentia ; Cholinesterase ; Piperidine derivatives ; Alkaloid ; Tic ; Pathophysiology ; Animal model ; Mechanism of action ; Nicotinic receptor ; Anticholinesterase agent ; Enzyme inhibitor ; Interaction ; Mouse ; Animal ; Biological activity ; Donepezil ; Nicotine ; Mecamylamine ; Gilles de la Tourette syndrome ;

Mots-clés français / French Keywords

Enzyme ; Hydrolases ; Esterases ; Carboxylic ester hydrolases ; Maladie dégénérative ; Encéphale pathologie ; Système nerveux central pathologie ; Système nerveux pathologie ; Vertebrata ; Mammalia ; Rodentia ; Cholinesterase ; Pipéridine dérivé ; Alcaloïde ; Tic ; Physiopathologie ; Modèle animal ; Mécanisme action ; Récepteur nicotinique ; Anticholinestérasique ; Inhibiteur enzyme ; Interaction ; Souris ; Animal ; Activité biologique ; Donépézil ; Nicotine ; Mécamylamine ; Gilles de la Tourette syndrome ;

Mots-clés espagnols / Spanish Keywords

Enzima ; Hydrolases ; Esterases ; Carboxylic ester hydrolases ; Enfermedad degenerativa ; Encéfalo patología ; Sistema nervosio central patología ; Sistema nervioso patología ; Vertebrata ; Mammalia ; Rodentia ; Cholinesterase ; Piperidina derivado ; Alcaloide ; Tic ; Fisiopatología ; Modelo animal ; Mecanismo acción ; Receptor nicotínico ; Anticolinesterasa agente ; Inhibidor enzima ; Interacción ; Ratón ; Animal ; Actividad biológica ; Donepezilo ; Nicotina ; Mecamilamina ; Gilles de la Tourette síndrome ;

Mots-clés d'auteur / Author Keywords

Donepezil ; Aricept ; Nicotine ; Mecamylamine ; DOI ; Head twitch ; Tourette syndrome ;

Localisation / Location

INIST-CNRS, Cote INIST : 16578, 35400011901411.0040